1. Field of the Invention
The invention is directed to certain chemotherapeutic materials useful in the treatment of viral infections and tumors associated with viruses. More specifically, the invention is directed to adenosine deaminase resistant antiviral purine nucleosides.
2. Description of the Prior Art
The antiviral nucleoside 9-.beta.-D-arabinofuranosyladenine (ara-A) was first synthesized in a program designed to produce anticancer agents. A major liability in the use of ara-A lies in the fact that the nucleoside is rapidly deaminated by a commonly occurring enzyme, adenosine deaminase. Deamination of ara-A renders it much less effective and high doses of the drug are required at frequent intervals. A major effort to circumvent the deamination problem employs the use of ara-A in combination with adenosine deaminase inhibitors. This approach presents a problem in that the Food and Drug Administration is reluctant to approve and physicians are reluctant to prescribe a compound that inhibits an enzyme with a normal body function. A more desirable approach to the development of a more active antiviral or antitumor agent involves the use of a deamination resistant ara-A derivative. The carbocyclic ara-A analogs described herein circumvent the major disadvantage of ara-A because they are completely resistant to degradation by adenosine deaminase.
Bennett et al (Mol. Pharmacol. 4, 208-217, 1968) and Hill et al (Chem. Abstracts, 75, 86554s, 1971) disclose certain carbocyclic ribonucleosides which are said to have biological activity, although not possessing antiviral properties. The 2' hydroxyls of these ribonucleosides are trans (or down) to the heterocyclic ring. The carbocyclic ribonucleosides are not resistant to adenosine deaminase. Shealy et al (J. Am. Chem. Soc. 91, 3075-83, 1969) and Holy (Nucleic Acids Res., Spec. Publ., Symp. Chem. Nucleic Acids Components, 3rd, 1975) disclose similar ribonucleosides.